Kupper TS, Fuhlbrigge RCImmune Surveillance in the skin: mechanisms and clinical consequences. Nat Rev Immunol 4:211-222

Department of Dermatology, Brigham and Women's Hospital, Harvard Institutes of Medicine, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.
Nature reviews. Immunology (Impact Factor: 34.99). 04/2004; 4(3):211-22. DOI: 10.1038/nri1310
Source: PubMed


The skin, as the primary interface between the body and the environment, provides the first line of defence against a broad array of microbial pathogens and trauma. In addition to its properties as a physical barrier, the skin has many active defence mechanisms. In this review, we discuss the interaction between the innate and adaptive immune systems in the skin as a model for immune function at epithelial-cell interfaces with the environment. How these mechanisms account for the robust nature of cutaneous immune surveillance and how their dysregulation drives the pathogenesis of inflammatory skin disorders and skin-based tumours are the subjects of this review.

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    • "the skin fibroblasts and dermal macrophages (Sourisseau et al., 2007; Couderc et al., 2008; Kam et al., 2009). This will lead to the first round of virus replication and trigger an initial host immune response to contain the virus at the skin (Kupper and Fuhlbrigge, 2004; Schilte et al., 2010). Despite the immune response, the virus rapidly disseminates into the lymph node before further dissemination to other tissues (e.g., muscles) via the circulatory system (Kam et al., 2009). "
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    • "The skin hosts a readily accessible network of dendritic cells [9] [10]. A large number of delivery devices have been developed for the transcutaneous delivery of antigens [11]. "
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    Vaccine 06/2015; 209(30). DOI:10.1016/j.vaccine.2015.05.089 · 3.62 Impact Factor
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    • "Microbes are first sensed by the innate immune system through pattern-recognition receptors (PRRs), which recognize microbe-associated molecular patterns (MAMPs) (Kawai and Akira, 2010). Both epithelial cells and resident innate immune cells in the skin express PRRs (Kupper and Fuhlbrigge, 2004; Lai and Gallo, 2008). Among PRRs, Toll-like receptors (TLRs) are a well-characterized family with distinct recognition profiles (Kawai and Akira, 2010). "
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    ABSTRACT: Skin is constantly exposed to bacteria and antigens, and cutaneous innate immune sensing orchestrates adaptive immune responses. In its absence, skin pathogens can expand, entering deeper tissues and leading to life-threatening infectious diseases. To characterize skin-driven immunity better, we applied living bacteria, defined lipopeptides, and antigens cutaneously. We found suppression of immune responses due to cutaneous infection with Gram-positive S. aureus, which was based on bacterial lipopeptides. Skin exposure to Toll-like receptor (TLR)2-6-binding lipopeptides, but not TLR2-1-binding lipopeptides, potently suppressed immune responses through induction of Gr1+CD11b+ myeloid-derived suppressor cells (MDSCs). Investigating human atopic dermatitis, in which Gram-positive bacteria accumulate, we detected high MDSC amounts in blood and skin. TLR2 activation in skin resident cells triggered interleukin-6 (IL-6), which induced suppressive MDSCs, which are then recruited to the skin suppressing T cell-mediated recall responses such as dermatitis. Thus, cutaneous bacteria can negatively regulate skin-driven immune responses by inducing MDSCs via TLR2-6 activation.
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